Subpopulations of lymphocytes may be defined via functional, morphologic and immunochemical differences. Included among the properties that distinguish thymus-derived (T) vs. bone marrow-derived (B) lymphocytes are the apparent presence or absence of receptor sites for specific substances (Fc of immunoglobulin, C'3, etc.) and the response of the involved cell type to interaction with mitogen (e.g. PHA, Con A, LPS). These differences between T and B cells presumably reflect discrepancies in the chemical composition and/or structural arrangement of the plasma membrane. B cells may be further divided into subpopulations on the basis of membrane immunoglobulin (IgG, IgM, etc.). More recently subpopulations of T cells have also been defined on a functional basis (suppressor vs. helper T cells). Investigations to date suggest that most, if not all, of the above subpopulations differ in their sensitivity to ionizing radiation. Thus: 1) irradiated B cells placed in tissue culture survive less well than T cells; 2) the capacity of irradiated cells to traffic in normal fashion is inhibited at lower dose levels for B cells than for T cells; 3) after whole body exposure to 800 rads, a proportionately greater number of T than B cells are mobilized via thoracic duct cannulation; although viable, these radioresistant T cells are unable to proliferate in response to alloantigens on transfer to F1 hybrids; 4) T and B cells activated to appropriate mitogens or antigens in vivo or in vitro are more resistant than their nonactivated counterparts to radiation-induced interphase cell death; 5) suppressor T cells appear to be more radiosensitive than helper T cells; 6) B cells demonstrate radiation-induced morphologic alterations at lower dose levels than do T cells; 7) cortisone-sensitive T and B lymphoid cell lines are more radiosensitive than cortisone-resistant lines; 8) a subpopulation of cytotoxic lymphocytes (T cells) is very resistant to radiation injury. The purpose of this project is twofold: expand the above observations on the radiosensitivity of defined population of lymphocytes; define the physical-chemical basis of these differences in radiosensitivity and thereby gain a better understanding of the pathogenesis of radiation-induced interphase death of lymphocytes.